More Ways to Lyophilize Samples
The use of freeze dryers extends from applications in academic labs to zoos. Moreover, this technology contributes to basic research and manufacturing. For example, scientists at a zoo might use a freeze dryer to increase the concentration of a tranquilizer so that it works for larger animals such as bears or even elephants. Likewise, researchers use freeze-drying techniques to study animal nutrition, including freeze-drying excrement as part of the process of determining the amount of calories an animal captures from the food it eats. These examples, though, provide only a glimpse of the many workflows that depend on freeze-drying.
In brief, the freeze-drying process, or lyophilization, dehydrates a sample to preserve it. For instance, pharmaceutical companies might lyophilize a drug solution, making a preserved freeze-dried powder. This can be put in a two-sided syringe—with the powder in one side and saline in the other—that combines the ingredients only before injection, thus increasing the shelf life of a product.
In fact, some of the first large-scale freeze-drying started in World War II. Getting enough plasma to Europe to treat soldiers who were injured in combat required extensive refrigeration. Often, a lack of resources prevented the plasma from staying frozen and some of it spoiled, which created a life-or-death situation in field hospitals. To make it possible to ship the plasma at room temperature, the United States Army started freeze-drying the plasma. Preserved through lyophilization, the plasma gained the shelf life that military medical units needed.
Explaining the process behind freeze-drying, Jenny Sprung, product manager at Labconco (Kansas City, MO), says, “It takes a solid frozen sample and removes the moisture from it, without passing through the liquid phase.” In that way, this sublimation-based process maintains the biological integrity of the sample and preserves it for storage.
The lack of heating in this process makes it particularly useful for heat-sensitive materials. For example, researchers use lyophilization in many processes that involve nucleic acids—DNA and RNA— such as sequencing.
Researchers can choose between freeze dryers that handle anywhere from half a liter to 100 liters. Manufacturing facilities, such as drug-making facilities, use the larger devices.
How a freeze dryer works, though, depends in part on the solution being lyophilized. “We’ve seen a move from aqueous-based samples to more solvent- based ones,” says Sprung. The solvent matters because freeze-drying requires the right collector temperature to ensure that the sample won’t melt back on the freeze dryer. For example, Sprung says, “We’re seeing more [high-pressure liquid chromatography] samples.” These use acetonitrile as the solvent, and it melts at –45 degrees Celsius. To lyophilize such samples, a freeze dryer needs a lower collection temperature.
Given the pace of changes in research, scientists often adjust protocols. Consequently, Sprung says, “My recommendation is that if you’re going to purchase a freeze dryer, think long term.” She points out, for example, that alcohols did not freeze-dry very well in the past because of their low freezing points, but Labconco makes freeze dryers that go down as far as –105 degrees Celsius, which works with some alcohols
Beyond freeze-drying at lower temperatures, the newest models include some additional features, such as allowing users to program the temperature to ramp up during a run. For example, the SMART freeze-drying technology from SP Scientific (Stone Ridge, NY) helps researchers develop new freezedrying protocols. Some of today’s freeze dryers even include a freezing step on the front end.
For anyone in the market for a new freeze dryer, Sprung says, “I recommend talking to a manufacturer first.” She adds that some customers just order a freeze dryer without talking to anyone, which doesn’t always work so well. “Many people who do that have had to exchange them,” Sprung says.
It’s worth taking the extra time at the start to get the best product because freeze dryers tend to last a long time. “We started manufacturing them in 1974,” Sprung says, “and we still have some of our first freeze dryers out there.” She adds that people still call for parts and service on her company’s earliest models. That brings up another consideration: a customer should select a company that looks strong enough to be around a few decades down the road, in case today’s newest freeze dryer needs parts and service many tomorrows from now.
In fact, scientists never know when they’ll need parts or service. From a user’s standpoint, Jordan J. Green, Ph.D., professor of biomedical engineering at Johns Hopkins University in Baltimore, Maryland, says, “I am mostly satisfied with the current products overall.” He adds, “The biggest improvement that matters to me is reliability. For example, my lab’s lyophilizer is currently being repaired due to a problem with the pump.”
Also, Thomas Anchordoquy, Ph.D., professor at the University of Colorado’s Skaggs School of Pharmacy and Pharmaceutical Sciences, would like to see a temporary power source with a surge protector as part of a freeze dryer. He says, “Currently, when we have a power spike, the lyophilizer program often shuts down.”
So both new and old freeze dryers will probably end up needing service at some point. This arises in part from the extensive use of these instruments in a lab, plus the fact that researchers tend to keep a freeze dryer in service for a long time—usually decades. That makes all the more reason for a researcher to carefully explore how a freeze dryer will be used and to talk to an expert about options before making a purchase. Likewise, finding the most versatile unit now could make a freeze dryer more likely to be useful in future protocols. This workhorse technology will probably stay around—in research and manufacturing— for many decades in the future.
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